Prenatal Stress, Methylation in Inflammation-Related Genes, and Adiposity Measures in Early Childhood: the Programming Research in Obesity, Growth Environment and Social Stress Cohort Study

Psychosom Med. 2018 Jan;80(1):34-41. doi: 10.1097/PSY.0000000000000517.


Objective: Maternal stress during pregnancy may influence childhood growth and adiposity, possibly through immune/inflammatory programming. We investigated whether exposure to prenatal stress and methylation in inflammation-related genes were associated with childhood adiposity in 424 mother-child pairs in Mexico City, Mexico.

Methods: A stress index was created based on four prenatally administered stress-related scales (Exposure to Violence, Crisis in Family Systems, State-Trait Anxiety Inventory, and Edinburgh Postnatal Depression Scale). We measured weight, height, body fat mass (BFM), percentage body fat (PBF), and waist circumference in early childhood (age range, 4-6 years). Body mass index (BMI) z scores were calculated according to World Health Organization standards. DNA methylation in gene promoters of tumor necrosis factor α, interleukin 8, and interleukin 6 (IL6) in umbilical cord blood were determined by pyrosequencing.

Results: An interquartile range increase in stress index (27.3) was associated with decreases of 0.14 unit in BMI z score (95% confidence interval [CI] = -0.28 to -0.005), 5.6% in BFM (95% CI = -9.7 to -1.4), 3.5% in PBF (95% CI = -6.3 to -0.5), and 1.2% in waist circumference (95% CI = -2.4 to -0.04) in multivariable-adjusted models. An interquartile range increase in IL6 methylation (3.9%) was associated with increases of 0.23 unit in BMI z score (95% CI = 0.06-0.40), 8.1% (95% CI = 2.3-14.3) in BFM, 5.5% (95% CI = 1.7-9.5) in PBF, and 1.7% (95% CI = 0.2-3.3) in waist circumference.

Conclusions: Prenatal stress was associated with decreased childhood adiposity, whereas cord blood IL6 methylation was associated with increased childhood adiposity in Mexican children.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiposity / physiology*
  • Body Mass Index*
  • Child
  • Child, Preschool
  • Cohort Studies
  • DNA Methylation / physiology*
  • Female
  • Fetal Blood / metabolism*
  • Humans
  • Inflammation / metabolism*
  • Interleukin-6 / metabolism*
  • Interleukin-8 / metabolism
  • Pregnancy
  • Prenatal Exposure Delayed Effects / metabolism*
  • Stress, Psychological / complications*
  • Tumor Necrosis Factor-alpha / metabolism
  • Waist Circumference / physiology*


  • CXCL8 protein, human
  • IL6 protein, human
  • Interleukin-6
  • Interleukin-8
  • TNF protein, human
  • Tumor Necrosis Factor-alpha